Hi Guys, I had a few questions that I have not been able to find a good source to read -
1. I wanted to know which drug levels need to monitored....Depakote, Tegretol, Lithium, Dilantin...anything else? Are also levels of antipsychotics/antidepressants monitored?
2. Also, when do we measure the level - right before the administering the dose?
3. Now, I saw that Depakote level was measured in the AM right before the dose; however, does this hold true even with Depakote ER (I saw the residents check the level in AM after the Depakote ER was given at night)
4. After how many days do we check the level initially and then subsequently?
Thank you very much and a Happy New Year!
1. The only one on that list that you HAVE to measure is lithium with it's narrow therapeutic index (I've never used dilantin psychiatrically, so wouldn't speak to that). Depakote levels are of questionable utility generally speaking (it's either working or not, and it's either causing side effects or not... but we still check levels to make sure, even though it's not clear that the levels correlate with efficacy in psychiatry). Tegretol, the biggest reason to check is that it auto-induces metabolism, so a level of 6 a week after you start it might turn into a level of 3.5 a month later, and it's helpful to track that a bit. A few other levels are commonly used. Nortryptiline levels are probably best correlated w/ clinical efficacy among antidepressants, though a few other tricyclic levels are monitored by some. Of course, sometimes levels are checked just to check for compliance, and I've seen prozac levels and lamictal levels checked before, even though there is no clinical correlate I'm aware of. AP-wise, generally I've only seen clozaril and norclozapine levels drawn, which are again of questionable usefulness, and the hematologic side effects are typically not level or dose dependent, and seizure threshold issues seem to be dose dependent but not necessarily level dependent. Still, there are general target levels that people shoot for (400-600, though variable), and levels at which concerns of toxicity (with or without clinical signs) will make folks worry (most will crap their pants above 900).
2. Depends on the drug. Typically we measure trough levels, right before the next dose, but it's not necessarily that simple by any means. Lithium levels are usually drawn in the AM 12 hours after the HS dose. Some do a slight level adjustment of 10% if the entire dose is given HS. Similarly, depakote and tegretol levels are drawn in the AM dose, as are the clozapine levels (though the schedule of clozapine dosing can be extremely variable, from once daily dosing to QID dosing divided unevenly).
3. According to the studies used to get VPA-ER approved, the drug is supposed to be given daily IN THE AM because peak is usually 10-16 hours after administration (just in time for bed). Still, either out of not knowing any better, patient preference, or simply wanting to avoid focus on GI side effects, most people dose it QHS reflexively. Now, "officially," the Depakote ER level should be drawn before the next dose, so as you wonder, the level drawn in the AM should be spuriously high, and the level should actually be drawn in the evening before the QHS dose if that's the schedule. Practically speaking, a few people in my class actually tried getting levels both in the AM and PM w/ HS dosing, and found remarkably little variation. Once VPA-ER is at "steady state" after enough half-lives, the variation just isn't significant enough to worry about.
4. It's not days, but
half-lives you want to worry about. Typically, we check levels after about 4-5 half-lives of the drug, because w/ regular dosing, 90-95% of steady-state is achieved, practically speaking no difference than steady state. For example, lithium has a half-life of about 20 hours, but we'll say 24 for sake of example. Let's imagine we chose the perfect dose to achieve a level of 1.0 on BID dosing. If you check a level after 1 day, the level would be 0.5. After two, it'd be 0.75. After 3, it would be 0.88. After 4, it would be 0.94, then about 0.97, etc. Some will actually check on day 3, because that gives you a fair estimate of what your steady state level will be as well. This is a bit theoretical and doesn't work out EXACTLY, because kidneys and livers are never that straight forward, and half-lives are generally a range, but it's good to know how to think about the question.
